Abstract
Nitration of the ortho position of tyrosine results in the formation of 3-nitrotyrosine. Nitration of tyrosine residues in proteins using tetranitromethane has been used extensively to investigate the role of tyrosine residues in the function of many proteins (1). However, the existence of tyrosine-nitrated proteins in vivo was not investigated until the discovery of a potential nitrating agent. It was shown that the major protein modification following the reaction of peroxynitrite with proteins is 3-nitrotyrosine (2). Peroxynitrite is an oxidant formed by the near diffusion-limited reaction between two free radicals, nitric oxide (NO) and superoxide (3). Inflammatory cells, endothelium, and, potentially, other cells generate peroxynitrite upon stimulation of NO and superoxide production (4–6). Therefore, we and others have explored the possibility of using 3-nitrotyrosine as a marker for peroxynitrite-mediated oxidative stress. Published data has provided evidence that 3-nitrotyrosine is formed in a variety of human diseases and animal models of disease (7–17). Endogenous-tyrosine nitration is almost certainly derived via enzymatically produced NO although NO itself is not a nitrating agent (7–9). Chemically, protein-tyrosine residues can be nitrated by tetranitromethane (1), nitric acid plus sulfuric acid (18), nitrogen dioxide (19), the acidification of nitrite (20), and the reaction of nitrite with hypochlorous acid (21). However, under pathophysiological conditions, it appears that peroxynitrite is the proximal species for the formation of protein nitrotyrosine in vivo (22) and that CO2 is a catalyst for peroxynitrite-mediated nitration of tyrosine residues (22–24) (see Fig. 1).
Chemical structures: Tyrosine, 3-nitrotyrosine, and 3-aminotyrosine.
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Gow, A.J., McClelland, M., Garner, S.E., Malcolm, S., Ischiropoulos, H. (1998). The Determination of Nitrotyrosine Residues in Proteins. In: Titheradge, M.A. (eds) Nitric Oxide Protocols. Methods in Molecular Biology™, vol 100. Humana Press. https://doi.org/10.1385/1-59259-749-1:291
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DOI: https://doi.org/10.1385/1-59259-749-1:291
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